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Effectiveness of Rituximab in Pediatric OMS Patients.

This study has been completed.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by:
National Pediatric Myoclonus Center
ClinicalTrials.gov Identifier:
NCT00244361
First received: October 24, 2005
Last updated: May 6, 2011
Last verified: May 2011
  Purpose

The purpose of this study is to reduce the symptoms of OMS by testing rituximab (Rituxan®), to remove B lymphocytes that make antibodies and trigger brain inflammation. Evidence suggests that autoimmune brain inflammation causes the symptoms of OMS. This study of blood and spinal fluid intends to find out what effect rituximab has on OMS and on the spinal fluid B-cells.

Rituximab targets and destroys B-cells, which make antibodies that can attack the brain and cause may OMS. It is infused through a vein over a period of several hours. Rituximab has been used widely and studied extensively since its approval in 1997 by the U.S. Food and Drug Administration (FDA) for non-Hodgkin's B-cell Lymphoma (NHL). Today, more than 300,000 patients have received rituximab, and it is part of more than 200 completed, ongoing, or planned clinical trials. Rituximab is not FDA-approved for OMS.


Condition Intervention Phase
Opsoclonus-myoclonus Syndrome
Opsoclonus
Myoclonus
Ataxia
Drug: rituximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Clinical Trial of Rituximab for Pediatric Opsoclonus-Myoclonus Syndrome

Resource links provided by NLM:


Further study details as provided by National Pediatric Myoclonus Center:

Primary Outcome Measures:
  • Determine the effectiveness & selectivity of rituximab at depleting CSF B-cells in OMS with intrathecal B-cell expansion. This requires CSF & blood lympocyte immunophenotyping prior to the first infusion & intervals for 1 year after the final infusion.

Secondary Outcome Measures:
  • Evaluate the clinical efficacy & safety of rituximab by clinical assessments, scoring of videotapes for neurological severity, and various blood tests prior to the first infusion and then at one, three, six, and twelve months post the final infusion.

Enrollment: 25
Study Start Date: June 2005
Study Completion Date: December 2007
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Detailed Description:

Opsoclonus-myoclonus syndrome (OMS) is a rare but pervasive, paraneoplastic neurological disorder, purported to be autoantibody-mediated. We demonstrated expansion of B-cells in cerebrospinal fluid (CSF) despite tumor resection, chemotherapy, or conventional immunotherapy. Whether B-cells can be purged from the CSF compartment with benefit to the patient is unknown. Targeting of CSF B lymphocytes represents a novel and valuable paradigm shift in the therapy of centrally-mediated paraneoplastic disorders. The objective of this preliminary study is to determine if rituximab, a monoclonal antibody against CD20+ B-cells, reduces or eliminates CSF B-cells in OMS and whether the reduction results in clinical improvement. B lymphocyte subsets and relevant T-cell subsets will be immunophenotyped in the CSF and peripheral blood of children with OMS by four-color dual-laser flow cytometry. Sixteen children with an increased percentage of CSF B-cells will be treated with rituximab 375 mg/m2 IV once weekly for four consecutive weeks and CSF testing will be repeated at six months with more frequent clinical evaluations and blood testing out to 12 months. Clinical outcome will be rated blindly from videotapes by an experienced observer using a validated 12-item motor evaluation scale and quantifiable parameters of sleep, behavior and motor function. Immunological outcome variables will include percentages of B-cell subsets and quantitative immunoglobulins. Post-treatment results will be compared to pre-treatment values statistically. If rituximab proves to be an efficacious and safe method of treating CSF B-cell expansion and the neurological syndrome, this study will lead to a phase II trial with the eventual aim of gaining FDA approval of rituximab for this indication.

  Eligibility

Ages Eligible for Study:   6 Months to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • written consent from parents
  • have symptomatic OMS
  • have CSF B-cell expansion (>1% B-cells)
  • adequate renal function as indicated by normal BUN [10-25 mg/dL] and creatinine [0.4-1.2 mg/dL]
  • adequate liver function, as indicated by up to 2x normal AST [0-35 U/L] and ALT [0-35 U/L].
  • men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months after completion of treatment

Exclusion Criteria:

  • treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (which ever is longer)
  • receipt of a live vaccine within 4 weeks prior to enrollment
  • previous treatment with Rituximab
  • prior antibody therapy (does not include IVIg) within past 6 months
  • history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
  • history of HIV (patients considered high risk will be screened)
  • history of hepatitis B and/or hepatitis C (patients considered high risk will be screened)
  • history of recurrent significant infection or history of recurrent bacterial infections
  • known active bacterial, viral fungal mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening
  • pregnancy (a negative serum pregnancy test should be performed for all women of childbearing potential within 7 days of treatment)
  • significant cardiac (symptomatic arrhythmias or symptomatic structural heart disease) or pulmonary disease (including obstructive pulmonary disease)
  • concomitant chemotherapy
  • hemoglobin: >13.5 gm/dL or <10.0 gm/dL
  • platelets: <100,000/mm or >500,000/mm K/cumm
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00244361

Locations
United States, Illinois
National Pediatric Myoclonus Center, Department of Neurology, SIU School of Medicine, 751 N Rutledge St
Springfield, Illinois, United States, 62794
Sponsors and Collaborators
National Pediatric Myoclonus Center
Genentech, Inc.
Investigators
Principal Investigator: Michael R Pranzatelli, M.D. National Pediatric Myoclonus Center
  More Information

Additional Information:
No publications provided by National Pediatric Myoclonus Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Michael R Pranzatelli, MD, National Pediatric Myoclonus Center/ SIU School of Medicine
ClinicalTrials.gov Identifier: NCT00244361     History of Changes
Other Study ID Numbers: IND #11,771, SCRIHS (04-112)
Study First Received: October 24, 2005
Last Updated: May 6, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by National Pediatric Myoclonus Center:
opsoclonus
myoclonus

Additional relevant MeSH terms:
Opsoclonus-Myoclonus Syndrome
Syndrome
Paraneoplastic Syndromes
Paraneoplastic Syndromes, Nervous System
Myoclonus
Central Nervous System Diseases
Cranial Nerve Diseases
Disease
Dyskinesias
Eye Diseases
Neoplasms
Neoplasms by Site
Nervous System Diseases
Nervous System Neoplasms
Neurodegenerative Diseases
Neurologic Manifestations
Ocular Motility Disorders
Pathologic Processes
Signs and Symptoms
Rituximab
Antineoplastic Agents
Antirheumatic Agents
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014